A phase I, first-in-human trial of KO-947, an ERK1/2 inhibitor, in patients with advanced solid tumors.

Background: KO-947, a potent, intravenously administered, extracellular signal-regulated kinase (ERK) inhibitor, has demonstrated activity in preclinical models. This phase I trial of KO-947 evaluated maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with relapsed/refractory solid tumors.

Materials And Methods: This multicenter, open-label, dose-escalation study evaluated KO-947 0.

Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small Molecule Reactivator.

Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. Here, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing anti-proliferative changes in tumor cells.

Efficacy of Zenocutuzumab in Fusion-Positive Cancer.

Background: Neuregulin 1 () fusions are recurrent oncogenic drivers found in multiple solid tumors. NRG1 binds to human epidermal growth factor receptor 3 (HER3), leading to heterodimerization with HER2 and activation of downstream growth and proliferation pathways. The efficacy and safety of zenocutuzumab, a bispecific antibody against HER2 and HER3, in patients with fusion-positive solid tumors are unclear.

Twenty-first century alienation and health: a research agenda.

Alienation has been used as a crucial concept to describe the negative psychosocial impacts that stem from the ways production and consumption are organised in Marxist and non-Marxist traditions. The psychosocial impacts it generates are mediated through stress pathways to increase non-communicable physical and mental illnesses. There has been little empirical research on the impact of alienation on health and ways in which the impact might be reduced.